AIPL1

Chr 17ADAR

AIP like 1 HSP90 co-chaperone

Also known as: AIPL2, LCA4

NCBI Gene: 23746 ENSG00000129221 UniProt: Q9NZN9 OMIM: 604392

AIPL1 encodes aryl-hydrocarbon interacting protein-like 1, which functions as a chaperone protein important in protein trafficking, folding and stabilization in photoreceptor cells. Mutations cause autosomal recessive Leber congenital amaurosis with onset at birth or in the first few months of life (accounting for approximately 20% of cases), as well as autosomal dominant cone-rod dystrophy and juvenile retinitis pigmentosa. The gene shows low constraint against loss-of-function variants (pLI <0.001), consistent with recessive inheritance being the primary disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Leber congenital amaurosis (LCA) is the most severe inherited retinopathy with the earliest age of onset and accounts for at least 5% of all inherited retinal diseases. Affected individuals are diagnosed at birth or in the first few months of life with nystagmus, severely impaired vision or blindness and an abnormal or flat electroretinogram. The photoreceptor/pineal-expressed gene, AIPL1, encoding aryl-hydrocarbon interacting protein-like 1, is located within the LCA4 candidate region. The encoded protein contains three tetratricopeptide motifs, consistent with chaperone or nuclear transport activity. Mutations in this gene may cause approximately 20% of recessive LCA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 1.073 OMIM phenotypes

Clinical Summary— AIPL1

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Gene-Disease Validity (ClinGen)

AIPL1-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

85 unique Pathogenic / Likely Pathogenic· 244 VUS of 615 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — AIPL1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.37

OE 0.63 (0.39–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.08Z-score

OE missense 0.99 (0.89–1.10)

235 obs / 238.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.39–1.07)

0≤0.351.4

Missense OE?0.99 (0.89–1.10)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 10 / 15.9Missense obs/exp: 235 / 238.4Syn Z: 0.31

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAIPL1-related Leber congenital amaurosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6744th %ile

GOF

0.75top 25%

LOF

0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

615 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic52

Likely Pathogenic33

VUS244

Likely Benign209

Benign39

Conflicting30

Pathogenic

Likely Pathogenic

244

VUS

209

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	38	8	6	0	52
Likely Pathogenic	13	16	4	0	33
VUS	7	177	54	6	244
Likely Benign	0	9	68	132	209
Benign	0	12	24	3	39
Conflicting	—				30
Total	58	222	156	141	607

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap AIPL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →